Retinopathy

Retinopathy

1 Overview

Summary and Quick Facts

  • The retina is a small area of light-sensing tissue at the back of the eye. A healthy retina is critical for clear vision. Retinopathy occurs when the retina becomes damaged.
  • The tiny blood vessels in the eye are delicate and retinopathy can be a sign of systemic vascular problems. Diabetes and high blood pressure are common causes of retinopathy because they damage blood vessels in the retina.
  • In this protocol, you will learn about the causes of retinopathy and how it is diagnosed and treated. Also learn about the importance of lifestyle and dietary habits that support the health of blood vessels in the eyes.
  • Benfotiamine and carnosine are supplements that may help prevent damage caused by elevated blood sugar when used alongside a healthy diet and exercise.

Retinal damage, known as retinopathy, can severely and permanently impair vision and even lead to blindness. Retinopathy is often reflective of vascular disease, such as that caused by elevated blood sugar levels (diabetic retinopathy) and high blood pressure (hypertensive retinopathy).

Fortunately, several scientifically studied integrative interventions, like B vitamins, astragalus, and Pycnogenol, can support the health of various structures in the eye and may improve symptoms of retinopathy.

Causes and Risk Factors

Diabetic retinopathy

  • People with Type 1 diabetes are more likely to develop diabetic retinopathy than people with type 2 diabetes.
  • Longer duration of diabetes, higher blood glucose levels, higher blood pressure, and insulin use are also associated with an increased risk of diabetic retinopathy.

Hypertensive retinopathy

  • Between 2% and 15% of people >40 years of age will have some signs of hypertensive retinopathy.
  • Non-diabetic African Americans were more likely than non-diabetic whites to develop hypertensive retinopathy; however, they were also more likely to have high blood pressure, which may explain the association.
  • Poorly controlled blood pressure and chronic kidney disease were both linked to a higher risk of retinopathy in non-diabetic individuals.

Signs and Symptoms

  • Often, especially in the early stages of retinopathy, there are no symptoms.
  • Many of the early signs of diabetic retinopathy can be detected by a doctor examining the retina with an ophthalmoscope.
  • When there are symptoms, a wide spectrum of vision problems may occur, ranging from mild blurriness to sudden and dramatic loss of vision, particularly in the case of retinal detachment or hemorrhage.

Conventional Treatment

  • For people with diabetic or hypertensive retinopathy, treating the underlying condition damaging the retina (high blood glucose or elevated blood pressure) will help prevent progression of the retinopathy.
  • One of the major goals when treating retinopathy is the destruction of dysfunctional, abnormal blood vessels. Two techniques that use this approach are cryotherapy and photocoagulation.

Novel and Emerging Therapies

  • Vascular damage in diabetic retinopathy may be caused by vascular endothelial growth factor (VEGF) or protein kinase C. Inhibitors of these proteins have been studied as treatments for diabetic retinopathy.
  • In clinical studies, one lipid-lowering medication – fenofibrate (Tricor®, Antara®, Lipofen®) – was found to reduce the risk of development and progression of diabetic retinopathy.

Lifestyle and Dietary Considerations

  • Both diabetic and hypertensive retinopathy can in part be prevented by lowering blood pressure. Reducing sodium intake; eating a diet rich in fruits, vegetables, legumes, and low-fat dairy; consuming alcohol in moderation only; and maintaining a healthy weight can help lower blood pressure.
  • Type 2 diabetics that use diet and exercise to achieve and maintain a healthy weight will often be able to lower their blood glucose and HbA1c levels. Other dietary strategies that can be beneficial include eating a consistent amount of carbohydrates at each meal and eating foods with a low glycemic index.

Integrative Interventions

  • B-vitamins: A study found that a combination of vitamin B12, folic acid, and pyridoxal-5’-phosphate (a form of vitamin B6) reduced retinal swelling and increased light sensitivity in individuals with diabetic retinopathy. Benfotiamine, a derivative of vitamin B1, may help combat the effects of glycation on the retina.
  • Vitamin A and carotenoids: A clinical trial found that diabetics with retinopathy had improved vision after daily supplementation with lutein and zeaxanthin for three months.
  • Carnosine: Carnosine, a compound comprising the amino acids histidine and beta-alanine, has been shown to counteract glycation of retinal tissue.
  • Astragalus: A comprehensive review of several published studies found that astragalus was able to protect visual acuity and reduce fasting blood glucose and triglycerides in individuals with diabetic retinopathy.
  • Curcumin: Subjects with diabetic retinopathy receiving curcumin as a daily supplement had less retinal swelling, improved visual acuity, and better blood flow in the retina.
  • Pycnogenol: A comprehensive review examining the benefits of Pycnogenol concluded that Pycnogenol helped slow progression of diabetic retinopathy, improved visual acuity in people with diabetes, improved the strength of capillaries, and reduced capillary leakage into the retina.

2 Introduction

Our visual interpretation of the world is dependent upon the healthy function of the retina, a layer of light-sensitive tissue in the rear interior of the eye. Subsequent to the admittance of light into the eye through the pupil, nerve impulses are transmitted from specialized cells in the retina called photoreceptors to the brain via the optic nerve; this retina-brain communication facilitates sight as we know it (Dugdale 2011; Marshall 1987). Retinal damage, known as retinopathy, can severely and permanently impair vision and even lead to blindness (Cunha-Vaz 1998; Buch 2001; Torpy 2007).

Unfortunately, the retina is very delicate, which makes it especially vulnerable to damage (Sim 2013; Heng 2013). Retinopathy is, to a large extent, a manifestation of damage to the tiny blood vessels that supply the retina. As such, retinopathy is often reflective of systemic vascular disease, such as that caused by elevated blood sugar levels and high blood pressure (Torpy 2007).

One of the most common causes of retinopathy is diabetes. Despite advances in screening and treatment, diabetic retinopathy is present in nearly 50% of the diabetic population at any time and likely occurs to some degree to nearly all people with diabetes (Tremolada 2007). Globally, 93 million people have diabetic retinopathy, making it one of the most common causes of vision loss among adults in developed nations (Heng 2013; Rosberger 2013). Most people with diabetic retinopathy do not have any symptoms until the late stages, at which point the efficacy of treatment may be limited (Fraser 2013).

Retinopathy can also occur in non-diabetics. Individuals with high blood pressure can develop hypertensive retinopathy (Wong 2004).

Retinopathy is generally a preventable condition (Simo 2014). However, conventional medicine often fails to encourage aging individuals to initiate specific dietary and lifestyle strategies to minimize retinopathy risk, instead waiting to address the condition after it manifests as visual impairment for those affected. Procedures utilized in the treatment of retinopathy have the potential to cause serious side effects or complications (Arrigg 1998; Smiddy 1999; Singh 2008).

Fortunately, several scientifically-studied integrative interventions can support healthy physiology of various structures in the eye and may reduce risk of retinopathy. Moreover, since the retina is metabolically very active, adhering to a nutrient-rich, plant-based, low-glycemic diet is important for ensuring this unique tissue gets the nutrients it needs to function optimally (Delahanty 2013; Vlassara 2014).

This protocol will focus primarily on diabetic and hypertensive retinopathy among adults. It will provide readers with additional background information about retinopathy and review conventional as well as emerging treatment options for this condition. The importance of diet and lifestyle in retinopathy prevention and management will be discussed as well, and several natural agents that may support retinal health will be outlined. Because elevated blood sugar and blood pressure are two leading causes of retinopathy among adults, readers are encouraged to review the protocols on High Blood Pressure and Diabetes in conjunction with this one.

3 Background

Several different circumstances can lead to retinopathy, but the most common among adults are chronically elevated blood sugar (diabetic retinopathy) and high blood pressure (hypertensive retinopathy).

Diabetic Retinopathy

Most vision loss associated with diabetic retinopathy is caused either by fluid buildup around the central area of the retina (macular edema) or complications from the formation of new but poorly functioning blood vessels, a process called neovascularization (Coscas 2010). Both processes are triggered by high blood glucose resulting from poorly-controlled diabetes (Crawford 2009). Chronic exposure to high blood sugar initiates biochemical and physiological changes that lead to blood vessel damage and retinal dysfunction (Cheung 2010).

One mechanism that leads to blood vessel dysfunction involves the metabolism of excess glucose in cells. As excess glucose accumulates and is processed within the cells, it causes additional water to move into cells and impairs cellular function, ultimately resulting in cellular stress and damage, leading to neovascularization (McCulloch 2013a; Lorenzi 2007).

Chronically high glucose levels lead to the formation of compounds called advanced glycation end products or AGEs. AGEs are compounds formed when sugars in the blood interact with proteins in the body and lead to damage. The resultant dysfunctional proteins (AGEs) damage blood vessels in the eyes (McCulloch 2013a; Tarr 2013). In addition to being formed inside the body as a consequence of elevated blood sugar, AGEs are also present in foods that typify the Western diet. Several protein-rich foods, especially meat, can become laden with AGEs when cooked at high temperatures via methods that utilize dry heat such as broiling or grilling. Evidence suggests these exogenous AGEs may play a significant role in several diabetic complications (Vlassara 2014).

In addition, blood vessels in the eyes of diabetics may be prone to occlusion, which contributes to further damage and may increase the risk of macular edema (McCulloch 2013a).

Decreased blood supply to the retina diminishes oxygen flow to retinal cells, a phenomenon known as hypoxia. In response, the body tries to create new blood vessels (ie, neovascularization). However, these new blood vessels are quite fragile, and as a result are prone to leakage and rupture, leading to hemorrhage and worsening of macular edema (Kollias 2010). Ultimately, this combination of macular edema and neovascularization leads to the damage of diabetic retinopathy.

Diabetic retinopathy is classified into two types – nonproliferative and proliferative (Tarr 2013).

  • Nonproliferative: With nonproliferative retinopathy, the process of neovascularization has not yet begun (Cummings 2008). As a result, retinal damage is due to damage to existing blood vessels, not from the formation of malfunctioning new ones.
    • One of the earliest signs of nonproliferative retinopathy is the presence of microaneurysms (ie, outward ballooning of the capillaries). Additional signs of nonproliferative retinopathy include nerve-fiber infarcts, which are areas of neuron death due to disrupted blood flow, hemorrhaging within the retina, and hard deposits (called exudates) within the retina (Kollias 2010).
  • Proliferative: The proliferative phase of diabetic retinopathy is marked by the development of abnormal vessels (neovascularization) as the body seeks to restore blood flow to the retina. Proliferative retinopathy can cause additional bleeding, fibrosis (accumulation of scar tissue), and retinal detachment. Proliferative retinopathy can also cause sudden vision loss if bleeding from the blood vessels blocks light from entering the retina (Tarr 2013; Cummings 2008; Kollias 2010).

Hypertensive Retinopathy

Hypertensive retinopathy occurs due to high blood pressure. Initially, mainly the small arteries (arterioles) in the retina constrict. Over time, however, these arterioles become damaged and the connective tissue that supports them breaks down. This leads to damage of the blood vessel-retina barrier, resulting in blood and blood lipids (fats in the blood) spilling from the blood vessels into the area around the retina, damaging it, and leading to swelling of a structure in the eye known as the optic disc. Also, the blood vessel damage disrupts blood flow to the retina, further injuring it (Wong 2004; McDonald 2010). In addition to damaging the retina, hypertensive retinopathy is also associated with an increased risk of stroke (Ong 2013).​

4 Causes and Risk Factors

Diabetic Retinopathy

Diabetic retinopathy occurs in individuals with diabetes, but there are a number of factors that increase the risk that a diabetic will develop the condition.

People with type 1 diabetes, which is believed to be caused by autoimmune destruction of insulin-secreting cells in the pancreas, are more likely to develop diabetic retinopathy than people with type 2 diabetes (Yau 2012; Kollias 2010).

One of the most important risk factors for diabetic retinopathy, regardless of the type of diabetes, is how well the diabetes is controlled. This is often measured by levels of a protein called hemoglobin A1c or HbA1c, which is representative of blood sugar levels over a 3 to 4 month period. Hemoglobin is the component of red blood cells that transports oxygen. When high blood sugar damages hemoglobin via a process called glycation, the resultant dysfunctional molecules are called hemoglobin A1c. Conventional sources suggest a HbA1c level of 4.8-5.6% or less is normal, and for diabetics, it is typically recommended that HbA1c levels be maintained at or below 6.5-7% (Yau 2012; Zhang 2010; Kollias 2010; LabCorp 2014). For type 1 diabetics, reducing HbA1c levels to 7.2% can reduce the incidence of diabetic retinopathy by 76%. In people with type 2 diabetes, lowering HbA1c levels by 11% led to a decreased need for a treatment called photocoagulation (Kollias 2010). In contrast, Life Extension® recommends that HbA1c concentrations should be kept below 5.7% to optimize health and reduce the risk of several age-related diseases; levels below 5.0% are even more ideal, but this may be difficult for many individuals to achieve.

Longer duration of diabetes, higher blood glucose levels, higher blood pressure, and insulin use are also associated with an increased risk of diabetic retinopathy (Yau 2012; Zhang 2010; Kollias 2010; Bertelsen 2013). Other risk factors include high cholesterol levels, kidney disease, obstructive sleep apnea, smoking, anemia, and major surgical operations or hospitalizations that can affect blood sugar control (Yanoff 2010).

Hypertensive Retinopathy

The fine, delicate blood vessels that supply the retina are vulnerable to stress caused by high blood pressure. Hypertensive retinopathy can also be observed in people without a clinical diagnosis of hypertension. Between 2% and 15% of people >40 years of age will have some signs of hypertensive retinopathy (Wong 2004). In a study, non-diabetic African Americans were more likely than non-diabetic whites to develop hypertensive retinopathy; however, they were also more likely to have higher blood pressure levels, which may explain the association (Wong 2003). Aside from a history of elevated blood pressure, patients with a history of stroke or coronary artery disease are more likely to suffer from hypertensive retinopathy (Wong 2003; Wong 2004). Poorly controlled blood pressure and chronic kidney disease were both linked to a higher risk of retinopathy in non-diabetic individuals (Grunwald 2012; Klein 2010).​

5 Signs and Symptoms

Often, especially in the early stages of retinopathy, there are no symptoms. The presenting symptom of retinopathy is vision loss, typically in both eyes (NEI 2012). A wide spectrum of vision problems are observed, ranging from mildly blurred vision to sudden and dramatic loss of vision, particularly in the case of retinal detachment or hemorrhage (Helbig 2002; Yanoff 2010).

Different manifestations of retinopathy will affect vision differently. For example, hemorrhaging over the retina will cause sudden vision loss sometimes described as “a curtain falling.” Resorption of blood from around the retina can cause floaters, which are small specks that can appear in the vision, while macular edema can cause a decrease in visual acuity that cannot be corrected with glasses or contacts (Fraser 2013). However, most people do not have symptoms until the late stages of retinopathy (Fante 2010; McCulloch 2013b). Many of the early signs of diabetic retinopathy can be detected by a doctor examining the retina. These signs include small aneurysms in the eye, “cotton wool spots” (which are caused by small areas of nerve death), flame-shaped hemorrhages, and “hard” exudates (Viswanath 2003; Kollias 2010; Kembhavi 2011).

6 Diagnosis

Retinopathy is diagnosed by examining the retina. Physicians can use a device called an ophthalmoscope, which allows them to look into the eye and see the retina (Polack 2012). Alternately, retinopathy can be diagnosed by taking photographs of the retina, which can then be analyzed for signs of retinal damage. The accuracy of these testing methods depends on the extent of the disease and skill of the practitioner; people concerned about retinopathy should see an ophthalmologist. For diabetics, annual eye examinations by an ophthalmologist are highly desirable (Prasad 1999). ​

7 Conventional Treatment

For people with diabetic or hypertensive retinopathy, treating the underlying condition damaging the retina (high blood glucose or elevated blood pressure) will help prevent progression of the retinopathy (Heng 2013; Koby 2014; Wong 2004). Aside from control of the underlying trigger of the retinal disease, there are multiple options for treating retinopathy.

One of the major goals when treating retinopathy is the destruction of dysfunctional, abnormal blood vessels. Two techniques that use this approach are cryotherapy and photocoagulation (Paysse 2013; Koby 2014). Cryotherapy involves freezing the peripheral retina through the eye, but this technique has largely been replaced by photocoagulation. With photocoagulation, heat from an argon laser is used on the damaged retinal area (Paysse 2013). One of two approaches are used for diabetic retinopathy; focal or scatter (pan-retinal) photocoagulation. Focal photocoagulation is used to seal leaking blood vessels in specific regions of the retina, while scatter photocoagulation is used to make many small laser burns to stop blood vessel growth over larger areas of the retina (Yanoff 2010).

Possible side effects of photocoagulation include bleeding in the eye (vitreous hemorrhage), traction and detachment of the retina, or accidental burns to the central retina which may lead to central vision loss. Vitrectomy, the surgical removal of the gel-like substance in the middle of the eye (called vitreous humor) and replacement with a clear solution can remove areas of hemorrhage, improve vision, and allow for the repair of detached retinas (Arrigg 1998; Smiddy 1999). The major indications for vitreous surgery are vitreous bleeding that does not subside and certain forms of retinal detachment (Singh 2008). ​

8 Novel and Emerging Therapies

VEGF Inhibitors

Vascular endothelial growth factor, also known as VEGF, is a protein thought to play a critical role in the neovascularization that causes the progression of retinopathy. Thus, compounds that inhibit the effects of VEGF, known as VEGF inhibitors, have been studied as a treatment for diabetic retinopathy and retinopathy of prematurity (a form of retinopathy that can occur in infants born prematurely). Because these drugs are designed to only work locally, they require injection into the vitreous to be effective (Arevalo 2013; Bandello 2012). Two VEGF inhibitors that have shown promising results in clinical trials are bevacizumab (Avastin®) and pegaptanib (Macugen®) (Tremolada 2007). VEGF inhibitors may be an effective adjunct to photocoagulation and other techniques, but more trials need to be done to determine if they are appropriate as an initial therapy for retinopathy (Fraser 2013; Arevalo 2013; Kumar, Gupta, Saxena 2012; Bandello 2012).

Protein Kinase C Inhibitors

Similar to VEGF, some of the vascular damage that occurs in the retina in diabetic retinopathy is caused by increased activity of a protein called protein kinase C. Inhibiting the activity of this enzyme via protein kinase C inhibitors may be effective for treating diabetic retinopathy. One of the first studied inhibitors, PKC412, improved visual acuity in patients with diabetic macular edema at an oral dose of 100 mg per day. Another orally administered compound, called ruboxistaurin, has been found to slow the development of vision loss in diabetics in clinical trials (Nawaz 2013; PKC-DRS Study Group 2005).

Lipid-Lowering Drugs

Many people with diabetes already take medications to lower their levels of cholesterol and other lipids. In addition to increasing the risk of coronary artery disease and stroke, elevated levels of lipids may also contribute to inflammation that can lead to progression of diabetic neuropathy. In clinical studies, one lipid-lowering medication – fenofibrate (Tricor®, Antara®, Lipofen®) – was found to reduce the risk of development and progression of diabetic retinopathy (Simo 2013). A study examining the effects of fenofibrate on complications of diabetes found that diabetics that took fenofibrate were less likely to require laser therapy to treat diabetic retinopathy (Nawaz 2013). Although the exact mechanism by which fenofibrate helps combat diabetic retinopathy is unclear, the drug is known to modulate several pathways involved in inflammation, angiogenesis, and cell survival, all of which may play a role in diabetic retinopathy (Noonan 2013). Combining fenofibrate with other lipid-lowering medications, such as simvastatin (Zocor®) may also be effective (Nawaz 2013). Because these lipid-lowering medications are already widely used, they represent an intriguing new strategy for treating retinopathy.

Photobiomodulation

Photobiomodulation is a promising therapy for retinopathy of prematurity because it may help prevent damage from occurring in at-risk infants. In an animal model of retinopathy of prematurity, exposure of the subjects to light with a wavelength of 670 nm (ie, close to infrared light in wavelength) reduced signs of retinopathy. This treatment is based on the idea that certain wavelengths of light may help protect the eye from damage. Light at this wavelength reduces nerve cell death, decreases the formation of abnormal blood vessels and bleeding in the retina, and maintains healthy retinal blood vessels (Natoli 2013; Tang 2013). Experiments in rodent models have also found that photobiomodulation may be helpful for treating diabetic retinopathy (Tang 2013). ​

9 Lifestyle and Dietary Considerations

Both diabetic and hypertensive retinopathy can in part be prevented by lowering blood pressure. There are a number of dietary interventions that can help people lower their blood pressure. Reducing sodium intake is beneficial for some people, as too much sodium can cause the body to retain water, thus raising blood pressure. A diet rich in fruits, vegetables, legumes, and low-fat dairy can also help reduce blood pressure. Finally, consuming alcohol in moderation only and maintaining a healthy weight can help lower blood pressure (Kaplan 2013). Numerous strategies for maintaining a healthy blood pressure are outlined in the High Blood Pressure protocol.

Diabetics can also reduce their risk of developing diabetic retinopathy by improving their blood glucose control. Type 2 diabetics that use diet and exercise to achieve and maintain a healthy weight will often be able to lower their blood glucose and HbA1c levels (Bweir 2009). Other dietary strategies that can be beneficial include eating a consistent amount of carbohydrates at each meal, eating foods with a low glycemic index, and consuming alcohol in moderation only and with food. All of these interventions can help keep blood glucose levels down and help prevent complications of diabetes, including retinopathy (Delahanty 2013). Tight blood glucose control can also help reduce the risk of retinopathy in people with type 1 diabetes (Fraser 2013). Life Extension has outlined several strategies for controlling glucose levels in the Diabetes protocol.

Minimizing intake of AGE-rich foods is also advisable. The dietary burden of AGEs can be mitigated by high-moisture, low-heat, and prolonged-duration cooking methods such as boiling, steaming, or stewing. Grilling, broiling, or other cooking methods that employ intense, dry heat to quickly cook foods should be avoided, as these preparation methods promote AGE formation (Vlassara 2014).

10 Integrative Interventions

Benfotiamine

Benfotiamine is a derivative of thiamine, also known as vitamin B1. Benfotiamine was shown to reduce AGE-triggered damage in the retina and throughout the body (Balakumar 2010). In an animal model of diabetes, benfotiamine administration prevented diabetic retinopathy by ameliorating inflammation and mitigating various pathways that facilitate tissue damage due to high blood sugar (Hammes 2003). In a different animal model of diabetes, benfotiamine and thiamine were able to reduce the buildup of AGEs in the retina and other tissues (Karachalias 2010). Supplementation with 300 mg of benfotiamine along with 600 mg of alpha-lipoic acid, both taken twice daily for 28 days, has also been shown to reduce AGE accumulation in people with type 1 diabetes (Du 2008).  

Carnosine

Carnosine is a compound primarily produced by skeletal muscle that is made from two amino acids (alanine and histidine). It is able to block the production of AGEs and mitigate oxidative stress and other complications of diabetes (Hipkiss 2009). In an animal model of diabetic retinopathy, carnosine supplements delayed cataract formation and protected retinal capillaries from high blood sugar damage by additional mechanisms aside from AGE inhibition. For example, researchers found that the protective effects of carnosine were associated with the prevention of the high blood sugar induced increase in a growth factor called Ang-2 (Ang-2 in combination with VEGF causes vascular damage and neovascularization) (Pfister 2011; Fagiani 2013). In another model of diabetic retinopathy, carnosine in combination with white willow bark extract, alpha-lipoic acid, and Ginkgo biloba protected retinal cells from damage (Bucolo 2013).

B-Vitamins

Vitamin B12 may be able to protect against retinopathy by helping to keep homocysteine levels low. Homocysteine is an amino acid that can damage blood vessels. Diabetics are especially sensitive to the vascular damage caused by high homocysteine levels, as diabetes can cause chemical changes in homocysteine that make this molecule more toxic (Rahman 2013). The enzyme that neutralizes homocysteine requires vitamin B12 to function; thus, vitamin B12 deficiency can cause elevated homocysteine levels and contribute to diabetic retinopathy (Satyanarayana 2011).

People suffering from diabetic retinopathy often have higher homocysteine levels and lower levels of vitamin B12, suggesting a link between vitamin B12 deficiency and diabetic retinopathy (Rahman 2013; Satyanarayana 2011). One study found that individuals with proliferative diabetic neuropathy had estimated homocysteine levels about 30% higher than control subjects (Lim 2012). In a similar study conducted on 300 subjects with type 2 diabetes, lower levels of vitamin B12 and folic acid were associated with elevated homocysteine levels, and homocysteine levels were especially high in a subset of the study population who had diabetic retinopathy (Satyanarayana 2011). Another study found that plasma total homocysteine levels were higher among 614 subjects who had retinal vascular disease compared to 762 control subjects (Cahill 2003).

Importantly, homocysteine levels may be increased and vitamin B12 levels depleted by some treatments for diabetes, such as metformin. This treatment-related deficiency in vitamin B12 may increase the risk of diabetic retinopathy, underscoring the importance of supplementation among diabetics (Sato 2013). Other B vitamins may also play a synergistic role in preventing diabetic retinopathy. A study found that a combination of vitamin B12, folic acid, and pyridoxal-5’-phosphate (a form of vitamin B6) had beneficial effects with respect to reducing retinal edema and increasing light sensitivity in individuals with nonproliferative diabetic retinopathy (Smolek 2013).

Green Tea

Green tea powerfully combats oxidative stress, which plays a considerable role in diabetic retinopathy. In an animal model of diabetic retinopathy, administration of green tea for 16 weeks normalized several markers of oxidative stress as well as inflammation. Green tea treatment also preserved the structural integrity of retinal cells (Kumar, Gupta, Nag 2012). Green tea may also be able to help diabetics improve their blood sugar control and may protect against AGEs (Tsuneki 2004; Ho 2010). Some of the compounds in green tea, particularly epigallocatechin gallate (EGCG) may be able to inhibit the abnormal formation of blood vessels that can contribute to retinopathy (Skopinski 2004; Rodriguez 2006).

Vitamin A and Carotenoids

Vitamin A and related compounds called carotenoids are essential for eye health and function. Vitamin A and its precursor, beta-carotene, are needed for cells in the eyes to absorb light. Other carotenoids, including lutein, zeaxanthin, and lycopene are also found in the eye and are essential for normal vision and to protect the eye from potentially damaging light rays and oxidative stress (Brazionis 2009; Hu 2011). Multiple studies have found that people with diabetic retinopathy have lower levels of lycopene, lutein, and other carotenoids compared to diabetics without retinopathy (Li 2010; Brazionis 2009; Hu 2011).

Studies have investigated vitamin A and the other carotenoids as potential retinopathy treatments. A clinical trial found that diabetics with nonproliferative retinopathy had improved vision after daily supplementation with 6 mg of lutein and 0.5 mg of zeaxanthin for three months (Hu 2011). A clinical trial found that intramuscular administration of 10,000 IU of vitamin A for at least two weeks helped improve retinal sensitivity in preterm infants, further supporting the potential protective effects of vitamin A against retinal damage (Mactier 2012).

Bilberry

Bilberry is a fruit related to the blueberry. It contains a variety of beneficial compounds called anthocyanins shown to support eye health (Kemper 1999; Bornsek 2012; Miyake 2012). Historically, bilberry jam was eaten by British pilots in WWII to improve their night vision, but bilberry may also be useful for treating retinopathy (Tracy 2007). Bilberry and bilberry extracts may mitigate neovascularization in the retina, which complicates retinopathy (Tracy 2007; Zafra-Stone 2007; Matsunaga 2010; Kemper 1999).

Zinc

Zinc is an essential mineral that can help reduce oxidative damage in the eye (Moustafa 2004). People with diabetic retinopathy often have lower zinc levels than healthy individuals (Praveena 2013; Miao 2013). Zinc supplementation may help prevent diabetic retinopathy and delay its progression. Zinc may also help improve glucose control, inhibit the growth of abnormal retinal blood vessels, and keep blood vessels from becoming damaged and leaky (Miao 2013). In a rat model of diabetes, zinc supplementation suppressed levels of VEGF, a chemical involved in neovascularization (Dong 2004; Miao 2013).

Astragalus

Astragalus is a Chinese herb used for many years in traditional Chinese medicine for immune support and for diabetes (Cheng 2013). This herb may be able to prevent diabetic retinopathy, in part by inhibiting the formation of AGEs (Motomura 2009). Clinical studies have suggested that this herb has benefits for improving vision and treating retinopathy in diabetics (Yan 2011; Cheng 2013). In one study, people injected with an extract of astragalus had improved vision and fewer clinical signs of diabetic retinopathy than control subjects (Yan 2011). A comprehensive review of several published studies found that astragalus was able to protect visual acuity and reduce clinical signs of diabetic retinopathy. In all cases, oral preparations of astragalus were used, though doses and supplement forms varied. Some studies used between 60 and 600 mL of an astragalus-containing liquid supplement, while others used between 4.5 and 12 g of astragalus pills (Cheng 2013).

Resveratrol

Resveratrol, a chemical thought to have anti-aging properties, can protect nerve cells from damage (Anekonda 2008). Multiple studies on animals have suggested that resveratrol may combat retinopathy. Studies in animal models of diabetes have found that resveratrol reduces oxidative damage and inflammation in retinal cells while also maintaining the health of existing blood vessels and suppressing the growth of new ones (Kim 2012; Yar 2012; Soufi 2012; Losso 2010). Resveratrol has also shown promise in animal models of retinopathy of prematurity (Kim 2010; Li, Jiang 2012). In addition, resveratrol may be effective at treating autoimmune retinopathy (Anekonda 2008).

Lipoic Acid

Alpha-lipoic acid, an antioxidant compound that improves insulin sensitivity in individuals with type 2 diabetes, may prevent diabetic retinopathy (Nebbioso 2013). It can help restore antioxidant defenses within retinal cells (Lin 2006). Studies in animal models of diabetes have found that administration of alpha-lipoic acid reduces the accumulation of molecules damaged by free radicals and helps protect blood vessels in the retina (Kowluru 2004; Roberts 2006). Lipoic acid also appears able to suppress production of growth factors involved in the formation of new blood vessels, which is a major feature involved in the progression of diabetic retinopathy (Nebbioso 2013).

Polyunsaturated Fatty Acids

Polyunsaturated fatty acids, including omega-3 fatty acids, play many roles in the body. There is some evidence that omega-3 fatty acids may play a key role in maintaining the health of the retina (Chew 2011). One omega-3 fatty acid (docosahexaneoic acid [DHA]) is found in very high levels in the retina, and reduced levels of DHA in the retina are associated with altered retinal function. Levels of DHA are conserved in the retina even during periods of low DHA intake, further emphasizing its importance in this tissue (Jeffrey 2001).

DHA has anti-inflammatory properties and may be able to counteract some of the inflammatory changes seen in diabetic retinopathy (Bazan 2011; Chen 2005). In addition, DHA serves as the precursor for a compound called neuroprotectin D1, which protects the eye against inflammatory damage and promotes the survival of cells within the retina (Bazan 2006; Mukherjee 2004). Neuroprotectin D1 also inhibits the growth of new blood vessels (Bazan 2011). DHA itself may combat the growth of abnormal blood vessels in the retina as well (Sapieha 2011). In animal models of diabetes, omega-3 supplementation helped prevent diabetic retinopathy (Tikhonenko 2013; Sapieha 2012).

Omega-3 fatty acids may also play a role in retinopathy of prematurity. During the third trimester of pregnancy, a large amount of long-chain polyunsaturated fatty acids are transferred across the placenta into the fetus. With premature birth, the infant’s reserves may not be sufficient, which could affect retinal development (Hard 2013). In animal models of retinopathy of prematurity, supplementation of the diet with omega-3 fatty acids protected against abnormal blood vessel development and retinopathy (Mantagos 2009; Chen 2011; Chew 2011; Hard 2013; Sapieha 2011). One clinical trial found that premature infants who received intravenous fish oil, which is rich in omega-3 fatty acids, had less laser surgery-requiring retinopathy (Pawlik 2013).

Curcumin

Curcumin is a compound found in turmeric, a spice commonly used in Indian cooking. It may be able to prevent some of the complications of diabetes, including retinopathy (Gupta 2011). Curcumin appears to be able to modulate the activation of multiple proteins involved in inflammation, including tumor necrosis factor-alpha (TNF-α) and COX-2, which play a role in the progression of diabetic retinopathy and other diseases of the eye (Srinivasan 2004). In animal models of diabetic retinopathy, curcumin was able to protect the cells in the retinal capillaries from damage and reduce the levels of VEGF, helping prevent neovascularization (Gupta 2011; Mrudula 2007). Curcumin also reduced markers of retinal inflammation in animal models of diabetic retinopathy (Kowluru 2007). In addition, it may prevent the hyperglycemia-induced proliferation of abnormal blood vessels in the eye (Rema 2007). One clinical trial examined the effects of 200 mg of curcumin daily on people diagnosed with diabetic retinopathy. Subjects receiving the curcumin supplement had less retinal swelling, improved visual acuity, and better blood flow in the retina (Steigerwalt 2012).

Pycnogenol

Pycnogenol, an extract of bark from the French maritime pine tree, has been studied as a treatment for diabetic retinopathy (Spadea 2001). One benefit of Pycnogenol is that it may help lower blood glucose levels. In addition, Pycnogenol may protect the capillaries in the retina from damage. One clinical trial studying 77 people with type 2 diabetes examined the effects of Pycnogenol on levels of endothelin-1, a marker for blood vessel damage. The 34 subjects given 100 mg of Pycnogenol daily for 12 weeks had reduced levels of endothelin-1 compared to the 43 given placebo (Liu 2004). A comprehensive review of multiple studies totaling 1289 people examining the benefits of Pycnogenol found that it could be useful for treating diabetic retinopathy. This article concluded that doses of Pycnogenol ranging from 60 to 150 mg helped slow progression of diabetic retinopathy, improved visual acuity in people with type 2 diabetes, improved the strength of capillaries, and reduced capillary leakage into the retina (Schonlau 2002). Another study examining the effects of 150 mg of Pycnogenol administered daily to type 2 diabetics over the course of two months found that the 24 subjects receiving Pycnogenol had improved visual acuity as well as less retinal swelling and thickening compared to the 22 people receiving placebo (Steigerwalt 2009). In addition to containing compounds that can neutralize retinal damage due to diabetes, some of the compounds in Pycnogenol may be able to help repair damaged capillaries (Spadea 2001).

Ginkgo Biloba

Ginkgo biloba extract is derived from the leaves of the Ginkgo biloba tree and contains over 60 bioactive compounds that may help promote human health (Oh 2013). It appears to prevent damage to cells in the retina from toxic chemicals that can damage neurons (Zaghlool 2012; Oh 2013). In addition, Ginkgo biloba extract helps improve circulation by inhibiting blood clots, improving the health of blood vessels, and making red blood cells more pliable, which allows them to circulate more freely (Oh 2013). As a result, Ginkgo biloba may be able to protect against diabetic retinopathy and retinopathy of prematurity. When combined with white willow bark, Ginkgo reduced inflammation and damage to retinal cells in an animal model of diabetes (Bucolo 2013). In a clinical trial, 240 mg of an extract of Ginkgo biloba daily improved retinal blood flow in people with type 2 diabetes when taken for three months (Huang 2004). Ginkgo biloba has also shown promise in preventing damage due to inadequate oxygen delivery (hypoxia), which is involved in retinopathy of prematurity. In both a cell culture and a rat model of retinopathy, a Ginkgo biloba extract prevented hypoxic damage and formation of abnormal blood vessels (Oh 2013; Juarez 2000). Ginkgo biloba should be used with care because its blood thinning capability can lead to an increased risk of bleeding, including retinal bleeding (Fraunfelder 2004).

Rosmarinic Acid

Rosmarinic acid is a substance that can be isolated from many different plants, including the Chinese medicinal herb Salviae miltiorrhizae, rosemary, and the Lamiaceae family of plants (Kim 2009; al-Sereiti 1999; Huang 2006). In addition to reducing inflammation and cell damage, rosmarinic acid may be able to prevent neovascularization. In a cell culture experiment, addition of rosmarinic acid prevented the formation of new blood vessels (Huang 2006). It also suppressed neovascularization in an animal model of retinopathy of prematurity (Kim 2009). Although more experiments are needed, this represents a promising avenue for further research for treating retinopathy. ​

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